The incidence of brain tumors in the U.S., including primary and metastases of other cancers, is estimated to be around 200,000 per year. Current treatments consist of open surgery, radiation, and chemotherapy, but these treatments are by no means curative for most patients and result in substantial side effects for some patients. There is a significant need for therapies that improve outcomes with fewer side effects than current therapies, but which are also synergistic with current approaches. We have previously completed a feasibility study of a minimally invasive, nanoparticle-directed, image- guided therapy for the photothermal ablation of solid tumors in a canine brain tumor model. This proposed research project will translate these preliminary studies into a clinical application and provide the basis for a human clinical trial at the conclusion of the project. Using a canine glioma cell line, we will demonstrate that systemically-delivered, infrared absorbing nanoparticles will self-select for the tumor boundary. Using Magnetic Resonance temperature imaging, we will demonstrate that the photothermal ablation can be confined to a tumor-specific treatment zone, resulting in clear margins with minimal damage to adjacent neural tissue. The selectivity of this therapy will be assessed by acute (48-72 hour) pathology and longer (6 week) survival studies. The minimally-invasive nature of the percutaneous photothermal treatment should lead to an enhancement of patients' quality of life as a result of reduced tumor volume and reduced intracranial pressure, which should reduce the incidence of seizures and headaches. And, a lowered morbidity in cancer patients would permit other treatments such as chemotherapy which do not conflict with this photothermal therapy. Additionally, a minimally invasive, percutaneously delivered photothermal therapy may permit treatment of non-resectable deeper or skull-based tumors. PUBLIC HEALTH RELEVANCE: The incidence of brain tumors in the U.S., including primary and metastases of other cancers, is approximately 200,000 per year. The currently accepted treatment modalities for tumors of the brain include surgery, whole-brain radiotherapy, stereotactic radiosurgery, chemotherapy; or some combination of these, but these treatments are by no means curative for most patients and result in substantial side effects for some patients. We will develop a minimally invasive therapy to eliminate or reduce in size primary tumors in the brain and skull, improving outcomes and reducing morbidity.